Quick Summary
- New, more effective treatment option available earlier in the disease course.
- 83% survival rate at 3 years shows durable benefit.
- Manageable side effects with proper monitoring.
- Free patient support program available.
Johnson & Johnson, a leader in multiple myeloma therapeutics, announced today that the U.S. Food and Drug Administration (FDA) has approved TECVAYLI® (teclistamab-cqyv) plus DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) for adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent.
This significant approval represents a transformative milestone in multiple myeloma treatment, offering a novel approach for addressing disease progression in an expanding patient population. The combination therapy activates the immune system to target and eradicate myeloma cells expressing BCMA (B-cell maturation antigen), with the potential to become a new standard of care as early as the second-line treatment setting.
Unprecedented Clinical Data Drives FDA Approval
The FDA’s decision was based on compelling results from the Phase 3 MajesTEC-3 trial, an international randomized study that evaluated the safety and efficacy of teclistamab plus daratumumab against investigator’s choice of standard-of-care regimens (daratumumab and dexamethasone with either pomalidomide or bortezomib) in patients with relapsed/refractory multiple myeloma.
Key Clinical Efficacy Endpoints
The MajesTEC-3 study demonstrated statistically significant improvements across all primary and secondary endpoints:
Progression-Free Survival (PFS):
- 83% three-year PFS rate with TECVAYLI plus DARZALEX FASPRO versus 30% in the control arm.
- 83% reduction in risk of disease progression or death (hazard ratio [HR] 0.17; 95% CI 0.12–0.23; P<0.0001).
- This substantial difference underscores the durable clinical benefit of the combination therapy.
Overall Response Rate (ORR):
89.0% ORR with TECVAYLI plus DARZALEX FASPRO compared to 75.3% with standard care (odds ratio [OR] 2.65; 95% CI 1.68–4.18).
Complete Response or Better (≥CR):
- 81.8% complete response rate versus 32.1% in the control group (OR 9.56; 95% CI 6.47–14.14).
- This represents a substantial improvement in achieving deep remissions.
Minimal Residual Disease (MRD) Negativity:
- 58.4% of patients achieved MRD-negativity with the combination therapy versus 17.1% in the control arm (OR 6.78; 95% CI 4.53–10.15; P<0.0001).
- MRD-negativity is an increasingly recognized predictor of improved patient outcomes.
Overall Survival (OS):
- 83.3% three-year OS rate with TECVAYLI plus DARZALEX FASPRO compared to 65.0% in the control arm.
- OS benefit favored the combination therapy across all prespecified subgroups (HR 0.46; 95% CI 0.32–0.65; P<0.0001).
Safety Profile and Tolerability
The safety analysis revealed that TECVAYLI plus DARZALEX FASPRO maintained a manageable and well-characterized toxicity profile comparable to standard-of-care regimens, supporting its use in broader patient populations:
Grade 3/4 Treatment-Emergent Adverse Events (TEAE):
- Similar incidence rates between the combination therapy (95.1%) and control regimen (96.6%).
- Most Grade 3/4 events were attributed to cytopenias and infections.
Cytokine Release Syndrome (CRS):
- 60.1% incidence of CRS in TECVAYLI plus DARZALEX FASPRO patients.
- All cases were Grade 1/2 in severity, indicating excellent tolerability.
- No treatment discontinuations due to CRS.
- Standard management protocols effectively controlled symptoms.
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS):
- Rare occurrence at 1.1% of patients.
- Demonstrates improved neurologic tolerability compared to monotherapy data.
- All ICANS events occurred during the step-up dosing schedule and were manageable.
Infections:
- Any-grade infections: 96.5% with TECVAYLI plus DARZALEX FASPRO vs. 84.1% with control
- Grade 3/4 infections: 54.1% vs. 43.4% respectively
- Notably, Grade 3+ infections declined significantly after the first 6 months of treatment with established immunoglobulin supplementation and infection prophylaxis protocols
Treatment Discontinuations:
- Low discontinuation rate due to adverse events: 4.6% versus 5.5% in the control arm
- Grade 5 (fatal) TEAEs: 7.1% with combination therapy vs. 5.9% with control regimen
This favorable safety profile enables broader clinical applicability and supports the potential for use earlier in the treatment paradigm.
Read More: European Commission Approves DARZALEX® for Treating High-Risk Smouldering Multiple Myeloma
Regulatory Milestone and Strategic Recognition
The FDA granted multiple designations highlighting the clinical importance of this approval:
- Breakthrough Therapy Designation: Recognizing the substantial improvement over existing treatments.
- Real-Time Oncology Review: Streamlining the review process based on robust clinical evidence.
- Commissioner’s National Priority Voucher (CNPV) Selection: The FDA proactively selected TECVAYLI’s supplemental Biologics License Application to participate in the CNPV Pilot Program, underscoring alignment with national priorities for delivering innovative therapies.
Amgen Tavneos NEJM Retraction: Medical Journal Pulls Pivotal Clinical Trial Paper For Amgen’s Rare-Disease Drug Tavneos
The New England Journal of Medicine has retracted the pivotal 2021 clinical trial paper for Amgen's rare-disease drug Tavneos (avacopan). The retraction follows an FDA […]
Roche AXELIOS 1: A Transformative Step for Next-Generation Sequencing Platforms Launched
Roche has officially announced the launch of AXELIOS 1, a next-generation sequencing platform built on proprietary SBX technology, promising same-day whole-genome sequencing with unprecedented speed […]
AstraZeneca Datroway EU Approval: CHMP Recommends Novel ADC for Metastatic Triple-Negative Breast Cancer
AstraZeneca and Daiichi Sankyo’s Datroway has received a positive CHMP recommendation in the European Union for the first-line treatment of adult patients with metastatic triple-negative […]
TECVAYLI’s Development Journey and Approval History
TECVAYLI represents a significant advance from earlier monotherapy approval:
- Initial FDA Approval: October 2022 for patients with four or more prior lines of therapy.
- Dosing Optimization: February 2024 approval for reduced dosing frequency (1.5 mg/kg every two weeks) in patients achieving a complete response or better.
- Current Approval: March 5, 2026, for second-line use in combination with DARZALEX FASPRO.
- Global Experience: More than 23,000 patients have been treated worldwide with TECVAYLI since approval.
- European Authorization: Conditional marketing authorization in August 2022, with subsequent approvals for reduced dosing frequency.
Comparison with Standard-of-Care Options
The MajesTEC-3 trial compared TECVAYLI plus DARZALEX FASPRO against two established standard-of-care regimens:
- Daratumumab + Pomalidomide + Dexamethasone (DPd)
- Daratumumab + Bortezomib + Dexamethasone (DVd)
Both control regimens are well-established, widely used options for relapsed/refractory multiple myeloma. The substantial superiority demonstrated in PFS, ORR, complete response rates, and OS against these proven standards underscores the clinical significance of the new approval.
Last Modified:
